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Author Notes:

Sanne J.H. van Rooij, PhD, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 69 Jesse Hill Jr Dr SE, Atlanta, GA 30303, USA, Tel: 404-251-8926, Fax: 404-778-1488. Email: sanne.van.rooij@emory.edu

van Rooij: conceptualization, methodology, formal analysis, investigation, writing-original draft, visualization, funding acquisition. Ravi: formal analysis, writing- original draft, visualization. Ely: software, methodology, formal analysis, writing- reviewing&editing. Michopoulos: investigation, project administration, data curation, supervision, writing- reviewing&editing. Winters: investigation, project administration, writing- reviewing&editing. Shin: software, methodology, funding acquisition, writing- reviewing&editing. Marin: methodology, writing- reviewing&editing. Milad: methodology, writing- reviewing&editing. Rothbaum: supervision, methodology, writing- reviewing&editing, funding acquisition. Ressler: supervision, resourcesmethodology, writing- reviewing&editing, funding acquisition. Jovanovic: conceptualization, methodology, supervision, resources, writing- reviewing&editing, funding acquisition. Stevens: conceptualization, methodology, validation, investigation, data curation, writing-original draft, supervision, funding acquisition.

We would like to acknowledge Lauren Hudak, M.D., Debra Houry, M.D., and Abigail HankinWei, M.D., for their collaborative efforts on this study. We would also like to thank Rebecca Hinrichs, Alex O. Rothbaum, Jessica Maples-Keller, Yvonne Ogbonmwan, Thomas Crow, Heather Grinstead, Devika Fiorillo, Renuka Reddy, Zachary Clifford, Adam Munoz, Erin Lightman-Renner, Lydia Odenat, Loren M. Post, Liza C. Zwiebach, Kathryn Breazeale, Jessica Morgan, Natasha Mehta, Elicia D. Skelton, Taleesha S. Booker, Jonathan Zebrowski, Siddharta Kosaraju, and Ariella Dagi for their work in the Emergency Department recruiting and assessing participants.

Dr. Ressler has received consulting income from Alkermes, research support from NIH, Genomind and Brainsway, and he is on scientific advisory boards for Janssen and Verily, all of which is unrelated to the present work. Dr. Rothbaum has funding from Wounded Warrior Project, Department of Defense Clinical Trial Grant No.W81XWH-10-1-1045, and McCormick Foundation. Dr. Rothbaum receives royalties from Oxford University Press, Guilford, APPI, and Emory University and received advisory board payments from Genentech, Jazz Pharmaceuticals, Nobilis Therapeutics, Sophren, Neuronetics, and Aptinyx. Dr. Rothbaum is a consultant to and owns equity in Virtually Better, Inc. that creates virtual environments. The terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict of interest policies, and is unrelated to the present work. Other authors report no potential conflicts of interest.

Subjects:

Research Funding:

This work was supported by Georgia State University/Georgia Institute of Technology Center for Advanced Brain Imaging (CABI) seed grant (to SVR and JS), National Institute of Mental Health Grant Nos. R01 MH094757 (to KJR), R21 MH106902 (to TJ), R01 MH117009 (to JSS) and R01 MH094757-01 (to BOR); and Brain and Behavior Research Foundation (National Alliance for Research on Schizophrenia and Depression) Distinguished Investigator Grant (to BOR).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Behavioral Sciences
  • Neurosciences
  • Neurosciences & Neurology
  • Emergency department
  • Trauma
  • Functional magnetic resonance imaging (fMRI)
  • Hippocampus
  • Posttraumatic stress disorder (PTSD)
  • Resilience
  • Fear conditioning
  • Fear extinction
  • Inhibition
  • Predictive biomarkers
  • Longitudinal study
  • Prospective study
  • POSTTRAUMATIC-STRESS-DISORDER
  • INACTIVATION DISRUPTS
  • EXTINCTION
  • MEMORY
  • PTSD
  • MODULATION
  • FMRI
  • ACQUISITION
  • VOLUME
  • SCALE

Hippocampal activation during contextual fear inhibition related to resilience in the early aftermath of trauma

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Journal Title:

BEHAVIOURAL BRAIN RESEARCH

Volume:

Volume 408

Publisher:

, Pages 113282-113282

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Impaired contextual fear inhibition is often associated with posttraumatic stress disorder (PTSD). Our previous work has demonstrated that more hippocampal activation during a response inhibition task after trauma exposure was related to greater resilience and fewer future PTSD symptoms. In the current study, we sought to extend our previous findings by employing a contextual fear conditioning and extinction paradigm to further determine the role of the hippocampus in resilience and PTSD in the early aftermath of trauma. Methods: Participants (N = 28) were recruited in the Emergency Department shortly after experiencing a traumatic event. A contextual fear inhibition task was conducted in a 3 T MRI scanner approximately two months post-trauma. Measures of resilience (CD-RISC) at time of scan and PTSD symptoms three months post-trauma were collected. The associations between hippocampal activation during fear conditioning and during the effect of context during extinction, and post-trauma resilience and PTSD symptoms at three-months were assessed. Results: During fear conditioning, activation of the bilateral hippocampal region of interest (ROI) correlated positively with resilience (r = 0.48, p = 0.01). During the effect of context during extinction, greater bilateral hippocampal activation correlated with lower PTSD symptoms three months post-trauma after controlling for baseline PTSD symptoms, age and gender (r=-0.59, p=0.009). Conclusions: Greater hippocampal activation was related to post-trauma resilience and lower PTSD symptoms three months post-trauma. The current study supports and strengthens prior findings suggesting the importance of hippocampus-dependent context processing as a mechanism for resilience versus PTSD risk, which could be a potential mechanistic target for novel early interventions.

Copyright information:

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/rdf).
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